title: Quantitative analysis of methylation status at 11p15 and 7q21 for the genetic diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.
abstract: Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). In this study, the efficacy of the MS pyrosequencing method at H19-DMR and LIT1-DMR at 11p15 and SGCE-DMR at 7q21 was evaluated for the genetic diagnosis of BWS (n=18) and SRS (n=20) patients. Epigenetic alterations or UPD were detected in 83% of BWS and 50% of SRS individuals by MS-MLPA, but the detection rate increased to 95% of BWS and 70% of SRS by MS pyrosequencing. Thirteen BWS patients (72%) harbored loss-of-methylation (LOM) at LIT1-DMR and two patients (11%) harbored gain-of-methylation (GOM) at H19-DMR, whereas two patients (11%) had both LOM at LIT1-DMR and GOM at H19-DMR, reflecting paternal UPD 11. Thirteen SRS patients (65%) harbored LOM at H19-DMR, whereas one patient (5%) had GOM at SGCE-DMR, reflecting maternal UPD 7. Birth anthropometric profiles were significantly correlated to methylation scores at either H19-DMR or LIT1-DMR. In conclusion, MS pyrosequencing enhanced the detection rate of molecular defects in BWS and SRS. Moreover, it indicates that methylation status at 11p15.5 might have an important role in fetal growth.
authors.affiliation: 1] Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea [2] Genome Research Center for Birth Defects and Genetic Disorders, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea [3] Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Beom Hee
authors.initials: BH
authors.lastname: Lee
authors.forename: Gu-Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: Tae Jeong
authors.initials: TJ
authors.lastname: Oh
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin-Joo
authors.initials: JJ
authors.lastname: Lee
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Choi
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: In Hee
authors.initials: IH
authors.lastname: Choi
authors.forename: Yoo-Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D010375:Pedigree; D056730:Silver-Russell Syndrome / Q000175:diagnosis / Q000235:genetics*